Future work is planned to determine the mechanisms of pyrogen production in vitro with both human and rabbit blood and tissue cells. We will use various activators, including a number of endogenous inflammogens, to correlate the production of endogenous pyrogen (EP), the messenger hormone that causes fever, with other aspects of cell activation. The possible role of PMN leukocytes and lymphocytes, as well as intracellular levels of cyclic AMP and GMP in modulating EP release from monocytes will also be investigated. The mechanisms of pyrogenic tolerance assocated with desensitization to specific antigen will be investigated. We will assay EP release in cell mixing experiments with tissues from tolerant and sensitized donors in order to determine whether suppressor-T cells play a role in this as in other immunologic phenomena.